Primary Bedaquiline Resistance Among Cases of Drug-Resistant Tuberculosis in Taiwan

Wu, Sheng-Han; Chan, Hsin-Hua; Hsiao, Hseuh-Chien; Jou, Ruwen

doi:10.3389/fmicb.2021.754249

Cited by 23 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 24 In three reports that used an MIC of ≥0.25 mg/L as the cut-off for resistance using the agar proportion method, the prevalence of primary BDQ resistance was 2.3% (8/347), 4.4% (4/90) and 3.1% (28/898). 12 , 23 , 26 …”

Section: Discussionmentioning

confidence: 99%

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan

Moe¹,

Rekart²,

Hernandez³

et al. 2023

int j tuberc lung dis

View full text Add to dashboard Cite

BACKGROUND: Bedaquiline (BDQ) is widely used in the treatment of rifampicin-resistant TB (RR-TB). However, resistance to BDQ is now emerging. There are no standardised regimens for BDQ-resistant TB. This study aims to share experience in managing primary BDQ-resistant TB.METHODS: We performed a retrospective study of patients treated for RR-TB in Karakalpakstan, Uzbekistan, from January 2017 to March 2022. We identified patients with resistance to BDQ with no history of BDQ exposure. We describe baseline characteristics, treatment and follow-up of these patients.RESULTS: Twelve of the 1,930 patients (0.6%) had baseline samples resistant to BDQ with no history of BDQ exposure, 75% (9/12) of whom had been previously treated for TB. Ten (83.3%) were resistant to fluoroquinolones; respectively 66% and 50% had culture conversion by Month 3 and Month 6. The interim treatment outcomes were as follows: unfavourable treatment outcomes (3/12, 25%), favourable outcomes (2/12, 17%); the remaining seven (58%) were continuing treatment.CONCLUSIONS: A large proportion of the cases had previously been treated for TB and had TB resistant to quinolone. Both patients who had not experienced culture conversion by Month 3 had an unfavourable treatment outcome. Therefore, we recommend monthly monitoring of culture status for patients on treatment regimens for BDQ resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan

Moe¹,

Rekart²,

Hernandez³

et al. 2023

int j tuberc lung dis

View full text Add to dashboard Cite

show abstract

“…Fourth, the phenotype-genotype reported in studies included in the analysis may not always be accurate due to lack of standardization of BDQ pDST and the use of the current critical concentration to determine the BDQ resistance phenotype [ 24 ]. This may especially be a problem for mutations that confer a modest increase in BDQ MIC, which overlaps with the wild-type MIC distribution [ 41 ]. Fifth, to maximally use all reported data on BDQ resistance given a specific mutation, data on clinical and non-clinical isolates was combined and analyzed.…”

Section: Discussionmentioning

confidence: 99%

A Bayesian approach to estimate the probability of resistance to bedaquiline in the presence of a genomic variant

Anlay

Rivière

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Background Bedaquiline is a core drug for treatment of rifampicin-resistant tuberculosis. Few genomic variants have been statistically associated with bedaquiline resistance. Alternative approaches for determining the genotypic-phenotypic association are needed to guide clinical care. Methods Using published phenotype data for variants in Rv0678, atpE, pepQ and Rv1979c genes in 756 Mycobacterium tuberculosis isolates and survey data of the opinion of 33 experts, we applied Bayesian methods to estimate the posterior probability of bedaquiline resistance and corresponding 95% credible intervals. Results Experts agreed on the role of Rv0678, and atpE, were uncertain about the role of pepQ and Rv1979c variants and overestimated the probability of bedaquiline resistance for most variant types, resulting in lower posterior probabilities compared to prior estimates. The posterior median probability of bedaquiline resistance was low for synonymous mutations in atpE (0.1%) and Rv0678 (3.3%), high for missense mutations in atpE (60.8%) and nonsense mutations in Rv0678 (55.1%), relatively low for missense (31.5%) mutations and frameshift (30.0%) in Rv0678 and low for missense mutations in pepQ (2.6%) and Rv1979c (2.9%), but 95% credible intervals were wide. Conclusions Bayesian probability estimates of bedaquiline resistance given the presence of a specific mutation could be useful for clinical decision-making as it presents interpretable probabilities compared to standard odds ratios. For a newly emerging variant, the probability of resistance for the variant type and gene can still be used to guide clinical decision-making. Future studies should investigate the feasibility of using Bayesian probabilities for bedaquiline resistance in clinical practice.

show abstract

“…78 Mutations in the atpE (Rv1305), pepQ (Rv2535c), and mmpR (Rv0678), Rv1979c genes of MTB confer resistance to BDQ. 29,79 Mutations in the atpE gene cause a high-level resistance to BDQ with the most frequently identified mutations being Ala63Pro and Ile66Met. 22,29,34,80 The other mutations occurring in atpE include Asp28Ala, Ala63Val, and Ile66Val.…”

Section: Drug Target Genes and Mutations Conferring Resistance To Bed...mentioning

confidence: 99%

“…22 Mutations in the Rv0678 gene cause a low-level cross resistance between BDQ and CFZ. 79 Similarly, mutations in the Rv2535c cause a low-level resistance to BDQ and CFZ. 79 Mutations in the pepQ gene confer cross-resistance between CLO and BDQ.…”

Section: Drug Target Genes and Mutations Conferring Resistance To Bed...mentioning

confidence: 99%

See 1 more Smart Citation

Drug-target genes and their spontaneous mutations associated with resistance to first-line, second-line, third-line, novel and repurposed anti-tuberculosis drugs in Mycobacterium tuberculosis resistant strains

Mumena

Kwenda²,

Ngugi³

et al. 2022

IJMMTD

View full text Add to dashboard Cite

Drug-resistant tuberculosis is a threat to the control of tuberculosis globally, it develops mainly due to mutations in target genes of (MTB). Mutations in the rpoB gene confer resistance to rifampicin (RIF). The most frequent mutations conferring resistance to RIF include; Ser531Leu, Asp516Val, and His526Asp. Isoniazid resistance (INHr) occur most frequently due to mutations in the and its promoter. Most frequent mutation in is Ser315Thr 1, while in inhA include; Thr8Cys, Ala16Gly, and Cys15Thr. Mutations in , and genes confer resistance to ethambutol. 70% of mutations in the gene occur in codon 306, 406, or 497 and include; Met306Leu, Gly43Cys, and Ser412Pro. Mutations in the , and genes mediate resistance to pyrazinamide. Frequent mutations in A include; Tyr64Ser, Phe94Ala, and Trp68Gly. MTB resistance to streptomycin (STR) occur due to mutations in the , B, and L genes. Mutations (Ala80Pro), and L (Lys43Arg) confer resistance to STR. Fluoroquinolone resistance is mediated via mutations in the A and B genes. The most common mutations in the A gene include; Gly88Cys, Ala90Val, and Ser91Pro. While those in the gyrB gene include; Glu540Val, and Asn538Asp. Mutations in the rrs and promoter region cause resistance to the kanamycin and amikacin. While mutations in the and A cause resistance to capreomycin and viomycin. Common mutations in include; Cys1402Thr, Ala1401Gly, and Gly1484Thr. While mutations in the include; Cys12Thr, Gly10Ala, and Gly37Thr.Detection of drug-target genes and their mutations has therapeutic and diagnostic value.

show abstract

Primary Bedaquiline Resistance Among Cases of Drug-Resistant Tuberculosis in Taiwan

Cited by 23 publications

References 47 publications

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan

A Bayesian approach to estimate the probability of resistance to bedaquiline in the presence of a genomic variant

Drug-target genes and their spontaneous mutations associated with resistance to first-line, second-line, third-line, novel and repurposed anti-tuberculosis drugs in Mycobacterium tuberculosis resistant strains

Contact Info

Product

Resources

About